Summary of Work: We have now completed studies showing that prophylactic treatment with granulocyte colony stimulating factor (G-CSF) reduces endotoxemia and serum tumor necrosis factor levels, and improves cardiovascular function and survival in both E. coli peritonitis and pneumonia in canine models. To determine whether prophylactic G-CSF would have similar effects with intravascular E. coli infection, we have investigated the effects of pretreating canines with G-CSF prior to E. coli infusion. In this study we found that in contrast to extravascular infection, G-CSF pretreatment was not associated with improvement in any parameter of outcome. Thus, stimulating neutrophil function may only be beneficial when circulating cells have an extravascular locus of infection to be recruited.